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New findings What is the topic of this review? We review biological and methodological factors associated with the variable changes in cardiorespiratory fitness in response to endurance training. What advances does it highlight? Several biological and methodological factors exist that each contribute, to a given extent, to response variability. Notably, prescribing exercise intensity relative to physiological thresholds reportedly increases cardiorespiratory fitness response rates compared to when prescribed relative to maximum physiological values. As threshold-based approaches elicit more homogenous acute physiological responses among individuals, when repeated over time, these uniform responses may manifest into more homogenous chronic adaptations thereby reducing response variability. Abstract Changes in cardiorespiratory fitness (CRF) in response to endurance training (ET) exhibit large variations, possibly due to a multitude of biological and methodological factors. It is acknowledged that ∼20% of individuals may not achieve meaningful increases in CRF in response to ET. Genetics, the most potent biological contributor, has been shown to explain ∼50% of response variability, whilst age, sex, and baseline CRF appear to explain a smaller proportion. Methodological factors represent the characteristics of the ET itself including the type, volume, and intensity of exercise, as well as the method used to prescribe and control exercise intensity. Notably, methodological factors are modifiable and, upon manipulation, alter response rates to ET, eliciting increases in CRF regardless of an individual's biological predisposition. Particularly, prescribing exercise intensity relative to a physiological threshold (e.g. ventilatory threshold) is shown to increase CRF response rates compared to when intensity is anchored relative to a maximum physiological value (e.g. maximum heart rate). It is, however, uncertain whether the increased response rates are primarily attributable to reduced response variability, greater mean changes in CRF, or both. Future research is warranted to elucidate whether more homogenous chronic adaptations manifest over time among individuals, as a result of exposure to more homogenous exercise stimuli elicited by threshold-based practices. This article is protected by copyright. All rights reserved.